CARBAMAZEPINE PHARMACOKINETICS IN YOUNG, ADULT AND PREGNANT RATS - RELATION TO PHARMACOLOGICAL EFFECTS

Abstract

Adult, male, female and pregnant rats were treated with single and repeated doses of carbamazepine (CBZ). The time course of the drug concentrations in plasma and tissues was followed. In all cases, data on plasma levels were subjected to pharmacokinetic analyses. Attempts were made to relate pharmacokinetic properties of carbamazepine to its effect on pentobarbital sleeping time and on protection against electroshock, after acute and repeated administration. Male rats eliminate carbamazepine faster than females: the total body clearance (TBC) was 16 ml/min per kg and 9.4 ml/min per kg, respectively. Two dose levels (25 and 50 mg/kg) had the same pharmacokinetic properties in young rats. Pregnant rats clear CBZ to a lesser extent than controls. CBZ accelerated its own elimination after repeated administration in both adult and young rats as revealed by the shortening of its half-life and an increase of 50% in clearance. The protection against electroshock was significantly reduced after repeated administration, compared with a single-dose administration. Repeated administration of CBZ in rats shortens pentobarbital sleeping time and decreases the pentobarbital brain level significantly.